Candidate's Plans/Training: The candidate plans a career as a patient-oriented researcher bridging pediatric medicine, sleep disorders, and genetics. Training will include formal epidemiology and biostatistics course work, structured laboratory work, and closely mentored completion of the research protocol. Environment: The outstanding pediatric research setting at UPCHP includes expertise in sleep disorders, clinical genetics, and molecular biology. These areas of strength will be complemented by the clinical and basic science research support offered by the Center for Sleep and Respiratory Neurobiology. Pennsylvania's Center for Clinical Epidemiology and Biostatistics will provide formal course training. Collectively, the environment is uniquely suited for this training award. Research: PLMS are rhythmic and highly stereotyped flexion movements of the extremities. PLMS may produce significant sleep disruption, and occur over a range of patient ages and settings. The pathophysiology of PLMS is unknown. Although family studies suggest a genetic basis for some cases of PLMS occurring with restless legs syndrome, no associated genes or gene products have been identified. Because preliminary data support the paucity of PLMS among control subjects and the prominence of PLMS in children with WS, this special group of patients may represent a unique opportunity to allow identification of a gene(s) involved in PLMS. WS is a human developmental disorder caused by a microdeletion of multiple genes in a distinct region of chromosome 7 (7q11.23). In this protocol, I propose to test the specific hypothesis that children with WS manifest genetically determined PLMS that is responsive to dopaminergic therapy. To this end, the primary aims of this proposal are: 1) to determine the prevalence of PLMS and the degree of variability in children with WS; 2) to determine whether PLMS are sensitive to dopamine therapy as are PLMS to other populations; and 3) to determine if there is a specific PLMS-genotype correlation in patients with WS. This protocol will provide new insights into WS as a model for PLMS in the general population, and may identify a specific gene(s) implicated in the etiology of these movements. Further, it will provide training necessary to conduct rigorous patient-oriented research in the area of genetics of sleep and its disorders.